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Protein

[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial

Gene

Pdk2

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Kinase that plays a key role in the regulation of glucose and fatty acid metabolism and homeostasis via phosphorylation of the pyruvate dehydrogenase subunits PDHA1 and PDHA2. This inhibits pyruvate dehydrogenase activity, and thereby regulates metabolite flux through the tricarboxylic acid cycle, down-regulates aerobic respiration and inhibits the formation of acetyl-coenzyme A from pyruvate. Inhibition of pyruvate dehydrogenase decreases glucose utilization and increases fat metabolism. Mediates cellular responses to insulin. Plays an important role in maintaining normal blood glucose levels and in metabolic adaptation to nutrient availability. Via its regulation of pyruvate dehydrogenase activity, plays an important role in maintaining normal blood pH and in preventing the accumulation of ketone bodies under starvation. Plays a role in the regulation of cell proliferation and in resistance to apoptosis under oxidative stress. Plays a role in p53/TP53-mediated apoptosis.5 Publications

Catalytic activityi

ATP + [pyruvate dehydrogenase (acetyl-transferring)] = ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate.6 Publications

Enzyme regulationi

Activity increases in response to increased acetyl-CoA and NADH levels and upon binding to the pyruvate dehydrogenase subunit DLAT. Inhibited by ADP and pyruvate; these compounds interfere with DLAT binding and thereby inhibit kinase activity. Inhibited by dichloroacetate. Inhibited by AZD7545; this compound interferes with DLAT binding and thereby inhibits kinase activity. Reactive oxygen species cause the formation of disulfide bonds, and thereby inhibit the enzyme.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei290ATP1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi251 – 258ATP8
Nucleotide bindingi309 – 310ATP2
Nucleotide bindingi325 – 330ATP6

GO - Molecular functioni

  • ATP binding Source: RGD
  • protein complex binding Source: RGD
  • protein heterodimerization activity Source: RGD
  • protein homodimerization activity Source: RGD
  • protein serine/threonine kinase activity Source: UniProtKB
  • pyruvate dehydrogenase (acetyl-transferring) kinase activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase

Keywords - Biological processi

Carbohydrate metabolism, Glucose metabolism

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.2. 5301.

Names & Taxonomyi

Protein namesi
Recommended name:
[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial (EC:2.7.11.2)
Alternative name(s):
PDK P45
Pyruvate dehydrogenase kinase isoform 2
Short name:
PDH kinase 2
Gene namesi
Name:Pdk2
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi69428. Pdk2.

Subcellular locationi

GO - Cellular componenti

  • mitochondrial pyruvate dehydrogenase complex Source: UniProtKB
  • mitochondrion Source: RGD
  • pyruvate dehydrogenase complex Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL2096663.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_0000023442? – 407[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial
Transit peptidei1 – ?MitochondrionSequence analysis

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei215PhosphotyrosineBy similarity1
Modified residuei216PhosphotyrosineBy similarity1
Modified residuei376N6-succinyllysineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

PRIDEiQ64536.

PTM databases

iPTMnetiQ64536.
PhosphoSitePlusiQ64536.

Expressioni

Tissue specificityi

Detected in heart (at protein level). Highest level of expression in heart and skeletal muscle and the lowest in spleen and lung. Liver, kidney, brain and testis levels are intermediate.3 Publications

Interactioni

Subunit structurei

Homodimer, and heterodimer with PDK1. Interacts with the pyruvate dehydrogenase complex subunit DLAT, and is part of the multimeric pyruvate dehydrogenase complex that contains multiple copies of pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (DLAT, E2) and lipoamide dehydrogenase (DLD, E3).4 Publications

GO - Molecular functioni

  • protein complex binding Source: RGD
  • protein heterodimerization activity Source: RGD
  • protein homodimerization activity Source: RGD

Protein-protein interaction databases

IntActiQ64536. 1 interactor.

Structurei

Secondary structure

1407
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi13 – 15Combined sources3
Helixi16 – 24Combined sources9
Helixi33 – 39Combined sources7
Beta strandi41 – 43Combined sources3
Helixi46 – 68Combined sources23
Helixi73 – 76Combined sources4
Helixi79 – 96Combined sources18
Turni97 – 100Combined sources4
Helixi106 – 122Combined sources17
Turni123 – 125Combined sources3
Helixi126 – 141Combined sources16
Helixi145 – 176Combined sources32
Beta strandi185 – 188Combined sources4
Beta strandi191 – 196Combined sources6
Helixi197 – 215Combined sources19
Beta strandi222 – 231Combined sources10
Beta strandi237 – 240Combined sources4
Helixi242 – 262Combined sources21
Beta strandi267 – 269Combined sources3
Beta strandi273 – 279Combined sources7
Beta strandi281 – 290Combined sources10
Helixi297 – 300Combined sources4
Helixi301 – 304Combined sources4
Turni306 – 309Combined sources4
Helixi329 – 339Combined sources11
Beta strandi343 – 349Combined sources7
Turni350 – 352Combined sources3
Beta strandi353 – 363Combined sources11
Turni364 – 366Combined sources3
Helixi376 – 380Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1JM6X-ray2.50A/B1-407[»]
3CRKX-ray2.30A/B1-407[»]
3CRLX-ray2.61A/B1-407[»]
ProteinModelPortaliQ64536.
SMRiQ64536.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ64536.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini135 – 364Histidine kinasePROSITE-ProRule annotationAdd BLAST230

Sequence similaritiesi

Belongs to the PDK/BCKDK protein kinase family.Curated
Contains 1 histidine kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Transit peptide

Phylogenomic databases

HOGENOMiHOG000164315.
HOVERGENiHBG000511.
InParanoidiQ64536.
KOiK00898.
PhylomeDBiQ64536.

Family and domain databases

Gene3Di1.20.140.20. 1 hit.
3.30.565.10. 1 hit.
InterProiIPR018955. BCDHK/PDK_N.
IPR003594. HATPase_C.
IPR005467. His_kinase_dom.
[Graphical view]
PfamiPF10436. BCDHK_Adom3. 1 hit.
PF02518. HATPase_c. 1 hit.
[Graphical view]
SMARTiSM00387. HATPase_c. 1 hit.
[Graphical view]
SUPFAMiSSF55874. SSF55874. 1 hit.
SSF69012. SSF69012. 1 hit.
PROSITEiPS50109. HIS_KIN. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q64536-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRWFRALLKN ASLAGAPKYI EHFSKFSPSP LSMKQFLDFG SSNACEKTSF
60 70 80 90 100
TFLRQELPVR LANIMKEINL LPDRVLSTPS VQLVQSWYVQ SLLDIMEFLD
110 120 130 140 150
KDPEDHRTLS QFTDALVTIR NRHNDVVPTM AQGVLEYKDT YGDDPVSNQN
160 170 180 190 200
IQYFLDRFYL SRISIRMLIN QHTLIFDGST NPAHPKHIGS IDPNCSVSDV
210 220 230 240 250
VKDAYDMAKL LCDKYYMASP DLEIQEVNAT NATQPIHMVY VPSHLYHMLF
260 270 280 290 300
ELFKNAMRAT VESHESSLTL PPIKIMVALG EEDLSIKMSD RGGGVPLRKI
310 320 330 340 350
ERLFSYMYST APTPQPGTGG TPLAGFGYGL PISRLYAKYF QGDLQLFSME
360 370 380 390 400
GFGTDAVIYL KALSTDSVER LPVYNKSAWR HYQTIQEAGD WCVPSTEPKN

TSTYRVS
Length:407
Mass (Da):46,106
Last modified:November 1, 1996 - v1
Checksum:iA01C377290A69EF4
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U10357 mRNA. Translation: AAB54084.1.
BC061823 mRNA. Translation: AAH61823.1.
PIRiA55305.
RefSeqiNP_110499.1. NM_030872.1.
UniGeneiRn.88597.

Genome annotation databases

GeneIDi81530.
KEGGirno:81530.
UCSCiRGD:69428. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U10357 mRNA. Translation: AAB54084.1.
BC061823 mRNA. Translation: AAH61823.1.
PIRiA55305.
RefSeqiNP_110499.1. NM_030872.1.
UniGeneiRn.88597.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1JM6X-ray2.50A/B1-407[»]
3CRKX-ray2.30A/B1-407[»]
3CRLX-ray2.61A/B1-407[»]
ProteinModelPortaliQ64536.
SMRiQ64536.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ64536. 1 interactor.

Chemistry databases

ChEMBLiCHEMBL2096663.

PTM databases

iPTMnetiQ64536.
PhosphoSitePlusiQ64536.

Proteomic databases

PRIDEiQ64536.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi81530.
KEGGirno:81530.
UCSCiRGD:69428. rat.

Organism-specific databases

CTDi5164.
RGDi69428. Pdk2.

Phylogenomic databases

HOGENOMiHOG000164315.
HOVERGENiHBG000511.
InParanoidiQ64536.
KOiK00898.
PhylomeDBiQ64536.

Enzyme and pathway databases

BRENDAi2.7.11.2. 5301.

Miscellaneous databases

EvolutionaryTraceiQ64536.
PROiQ64536.

Family and domain databases

Gene3Di1.20.140.20. 1 hit.
3.30.565.10. 1 hit.
InterProiIPR018955. BCDHK/PDK_N.
IPR003594. HATPase_C.
IPR005467. His_kinase_dom.
[Graphical view]
PfamiPF10436. BCDHK_Adom3. 1 hit.
PF02518. HATPase_c. 1 hit.
[Graphical view]
SMARTiSM00387. HATPase_c. 1 hit.
[Graphical view]
SUPFAMiSSF55874. SSF55874. 1 hit.
SSF69012. SSF69012. 1 hit.
PROSITEiPS50109. HIS_KIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPDK2_RAT
AccessioniPrimary (citable) accession number: Q64536
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: November 1, 1996
Last modified: November 2, 2016
This is version 132 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.